Method of manufacturing capsules containing gaseous radioisotope

ABSTRACT

A method of manufacturing capsules containing a gaseous radioisotope with a diluent is presented having the steps of (a) introducing the radioisotope and the diluent into a mixing zone, (b) mixing the radioisotope and the diluent in the mixing zone, (c) discharging the mixture into a gas impermeable enclosure, (d) sealing the gas impermeable enclosure into segments of a selected size and (e) separating the segments into individual capsules. It is also possible to manufacture capsules containing moisture in addition to the radioisotope-diluent mixture.

United States Patent [191 Lewis METHOD OF MANUFACTURING CAPSULES CONTAINING GASEOUS RADIOISOTOPE [75] Inventor: Robert E. Lewis, Pleasanton, Calif.

[73] Assignee: General Electric Company, San

Jose, Calif.

[22] Filed: Aug. 15, 1973 [2i] Appl. No.: 388,488

[52] U.S. Cl. 53/5; 53/21 FC; 53/37; 424/1 [5 l] Int. Cl B65b 29/00 [58] Field of Search 0. 53/3, 5, 21 FC, 22 A, 37; 424/1 [56] References Cited UNITED STATES PATENTS 3,040,490 Virta 53/22 A [451 July 8,1975

3,376,688 4/1968 Takacs et al 53/21 FC Primary ExaminerTravis S. McGehee Attorney, Agent, or Firm-lvor J. James, Jr.; Sam E. Laub; Samuel E. Turner [5 7] ABSTRACT A method of manufacturing capsules containing a gaseous radioisotope with a diluent is presented having the steps of (a) introducing the radioisotope and the diluent into a mixing zone, (b) mixing the radioisotope and the diluent in the mixing zone, (c) discharging the mixture into a gas impermeable enclosure, ((1) sealing the gas impermeable enclosure into segments of a selected size and (e) separating the segments into individual capsules. [t is also possible to manufacture capsules containing moisture in addition to the radioisotope-diluent mixture.

16 Claims, 2 Drawing Figures METHOD OF MANUFACTURING CAPSULES CONTAINING GASEOUS RADIOISOTOPE BACKGROUND OF THE INVENTION This invention relates to an apparatus for dispensing single doses of gaseous radioisotopes to a patient.

Radioactive isotopes of xenon and other radioisotopes are useful in the field of medicine and particularly in medical diagnosis. There is increasing use of xenon-133 in the medical field for studying blood flow in muscles, scanning the lungs for lung functional disorders (e.g., emphysema and emboli), scanning the brain and scanning for cardiac abnormalities. For scanning of the lungs, xenon-l33 can be introduced into a human body by one of two processes. ln an inhalation process, the patient breathes a gas containing xenon-I33 and the xenon-133 is drawn directly into the patients lungs. In an injection process, a saline solution containing dissolved xenon-l33 is injected into the blood stream of the patient and through perfusion the xenon-133 goes to various organs of the patient, including the patients lungs. Radioactive gases having more optimum imaging characteristics for specific purposes may also be used, such as xenon-127.

One current practice of formulating a xenon-133 solution for medical applications is to dissolve the xenonl33 directly into a saline solution to achieve gas concentrations appreciably below saturation of the xenon- ]33 in the solution at the temperature of dissolution. This avoids any occurrence of bubble formation in the solution during use. In further detail, the present procedure used in the medical profession for preparing injectable doses of xenon-I33 as an aqueous solution involves crushing an ampoule containing xenon-l 33 in a container filled with a normal saline solution.

The difficulties in handling and storage of xenon and in particular of a radiopharmaceutical xenon-l 33 solution are set forth in the Journal of Nuclear Medicine in Volume 1 l at page 352 (1970) and Volume 13 at page 231 (l972). These difficulties can be summarized as follows: (a) there is loss of xenon-133 into air spaces resulting as individual doses are removed from multidose vials since it is difficult to prevent the introduction of air bubbles when replacing the volume withdrawn from the vial; (b) there is diffusion of xenon-133 into rubber components in contact with the xenon-133 such as in elastomeric systems at the end of cylindrical glass capsules and rubber septums on multidose vials; and there is diffusion of xenon-l33 into both the plastic and rubber components of disposable syringes used for injection of the patient.

Studies have been made regarding the trapping of radioactive xenon in various materials, and these studies show that elastomers and a variety of materials will take up significant quantities of radioactive xenon. As a result of these studies, only glass syringes, which take up less than 1% of the xenon-I33 from the solution, are used for dispensing such radioactive xenon solutions. However it has remained desirable to minimize the foregoing difficulties and to further reduce the loss of radioactive xenon isotopes to the materials used to package doses of the radioactive xenon isotopes.

The widest use of xenon-I33 is in pulmonary function studies and this involves having the patient inhale a dose of gaseous xenon-133, and while the patient holds his breath a scintillation camera is used to take a picture of the patients lungs. This picture shows any portions of the patients lung not functioning or not properly functioning.

The use of xenon-I33 in pulmonary function studies has required quantities of xenon in patient dosage sizes accurately measured and readily administered to the patient. There have been several devices designed for holding and administering dosage sized quantities of gaseous radioactive xenon to patients, and such devices have the following requirements, namely ease and safety in administration to the patient; effective radiation shielding during shipment, storage and handling incidental to administration to the patient; a container insuring substantial retention of the radioactive xenon prior to administration to the patient; a container suitable for re-collection of the radioactive xenon after administration to the patient; a system capable of providing multiple administrations to the patient; absence of absorption of the radioactive xenon by the container holding the dosage size quantity of radioactive xenon; and a dispensing device providing high concentration of xenon in one inhalation.

One device for holding and administering dosage sized quantities of gaseous radioactive xenon is a Calidose gas dispenser. This dispenser unit is loaded with a glass vial closed off with an elastomeric septum and the glass vial holds the gaseous xenon prior to administration to a patient. The dispenser unit has a manually operated plunger for pushing the septum in the glass vial against two hollow needles and for puncturing the septum. A manually operated rubber squeeze bulb is connected to one hollow needle and flushes the xenon from the glass vial through the other hollow needle into a nozzle and into a breathing apparatus held in the patients mouth. This unit has a portion of the radioactive xenon absorbed by the estomeric septum.

Another device for discharging quantities of gaseous radioactive xenon is shown and described in Volume 92 of Radiology at pages 396-7 (February 1969). A gas cylinder containing radioactive xenon is filled with carbon dioxide to a pressure of three atmospheres giving a xenon-carbon dioxide mixture in the cylinder. A small quantity of the mixture is withdrawn from the cylinder through a micrometer needle valve. The amount of xenonl33 dispensed can be measured by placing the syringe inside a calibrated well-type ionization chamber. Radioactive xenon gas which is to be used in a closed-circuit spirometer system can be taken up into a Hamilton gas-tight syringe for transfer.

Another procedure is to use a hypodermic syringe to inject air into an ampoule sealed by a septum containing radioactive xenon and then to withdraw a fraction of the air-xenon mixture. The syringe is exhausted into a closed-circuit spirometer and the patient breathes the gases in the closed-circuit spirometer. This also has the septum absorbing a portion of the radioactive xenon.

Accordingly it has remained desirable to have a xenon dosage dispensing apparatus for patients providing a patient sized dose of radioactive xenon.

A particular desirable xenon dispensing apparatus is presented in a co-pending U.S. Pat. application Ser. No. 388,489, filed Aug. 15, 1973. This dispensing apparatus, also called a ventilation study system, has 1) an internal gas-retaining volume, (2) a shearable capsule containing a gaseous radioisotope, (3) valve means holding the capsule within an interior cavity forming a portion of the gas-retaining volume of the ventilation study system, shielding the radioactivity emitted from the radioisotope and being capable of shearing the cap.- sule to release the gaseous radioisotope into the gasretaining volume defined by the system, (4) patient breathing means in communication with the internal cavity of the valve means and a breathing bag defining a portion of the gas-retaining volume of the system and in communication with the internal cavity of the valve means. The shearable capsule is presented in copending U.S. Pat. application Ser. No. 388,700, filed Aug. 15, I973 and is a very important component of this ventilation system. The capsule has a gas impermeable enclosure holding a gaseous radioisotope with one preferred embodiment of the radioisotope being xenon, such as xenon-I33 and xenon-127. The capsule has to be readily shearable by the valve means of the ventilation system covered in co-pending US. Pat. application Ser. No. 388,487, filed Aug. l5, I973 and now abandoned in favor of copending continuation application Ser. No. 549,784, filed Feb. I3, I975, but must also be gas impermeable so that the gaseous radioisotope is contained within the capsule without loss of any of the radioisotope such as by diffusion through the enclosure. Accordingly there is a need for assembling the capsule by a very reliable, accurate method to give a shearable capsule of low unit cost.

SUMMARY OF THE INVENTION A shearable capsule particularly suitable for use with the ventilation study system disclosed in co-pending US. Pat. application Ser. No. 388,489 is produced by the method of this invention. This invention gives a very reliable, accurate method of producing the shearable capsule with a low unit cost. The method includes the steps of (I) introducing the gaseous radioisotope and the diluent into the mixing zone, (2) mixing the radioisotope and the diluent in the mixing zone, (3) discharging the mixture of (2) into a gas impermeable enclosure, (4) sealing the gas impermeable enclosure into segments of a selected size and (5) separating the segments into individual capsules. An additional step of adding moisture to the gas impermeable enclosure can be practiced along with the filling of the gas impermeable enclosure with the mixture. A particularly preferred gaseous radioisotope is xenon including xenon-l 33 and xenon-I27.

Accordingly it is an object of this invention to provide a method of producing a shearable capsule containing a mixture of a gaseous radioisotope and a diluent.

A further object of this invention is to provide a method of mixing a radioisotope and a diluent to give a useful radioisotope-diluent mixture and then introducing a selected quantity of this mixture into a gas impermeable enclosure.

Another object of this invention is to provide a method of producing a shearable capsule having a gas impermeable enclosure containing a mixture of a gaseous radioisotope, a diluent and moisture with the moisture being provided to eliminate any traces of undesirable gas resulting from radiation degradation of the enclosure.

Still another object of this invention is to provide a method of producing a capsule having a gas impermeable enclosure containing a gaseous radioisotope including the steps of introducing a selected amount of the gaseous radioisotope into a mixing zone, introducing a selected amount of a gaseous diluent into the mixing zone, mixing the radioisotope and the diluent in the mixing zone, discharging the radioisotope-diluent mixture into the gas impermeable enclosure sealed on one end, sealing the gas impermeable enclosure into segments of a selected size and separating the segments into individual capsules.

Other objects and advantages of this invention will become apparent to the person skilled in the art from reading the following specification, the appended claims and by reference to the drawings described immediately hereinafter.

DESCRIPTION OF THE DRAWINGS FIGS. 1 and 2 present in schematic form two embodi' ments of the apparatus used to produce radioisotope capsules according to the method of this invention.

FIG. 1 is adapted to receiving small glass ampoules as the source of the radioisotope and;

FIG. 2 is adapted to have a large gas cylinder connected to the apparatus as the source of the radioisotope.

DESCRIPTION OF THE INVENTION Referring to FIG. 1 there is shown one embodiment of a capsule manufacturing apparatus generally designated by the number 10 for manufacturing capsules containing a gaseous radioisotope. The capsule loading apparatus 10 has a mixing vessel 1 1 serving as a portion of a mixing zone for the gaseous radioisotope and the diluent. The mixing vessel 11 has a movable piston 13 for removing the gas from the mixing vessel 11. A line 12 runs from the mixing vessel 11 to chamber 14, and line 12 has valve 15 and screen 16 (a 200 mesh screen) between chamber 14 and mixing vessel 11. Chamber 14 has a screw piston 17 which can be screwed against the top plate 42 and the bottom of chamber 14. Line 12 further has a screen 18 (a 200 mesh screen), valve 19 and a pressure/vacuum gauge 20 before the junction of line 12 with line 21 which has valve 22. Line 12 further has valve 24 between the connection of line 12 with line 21 and the connection of line 12 with line 25. Evacuation line 25 has two valves 26 and 28 positioned before a pressure gauge 29 and a vacuum pump 30. Line 31 runs between line 25 and a supply 33 of a diluent (e.g. medical grade air) with valve 32 being provided for metering the diluent into line 25.

Line 12 has a 0.45 micron filter 36 before the connection of line 12 with loading line 37. Line 37 is connected with a source 38 of purified water which feeds an automatic pipette syringe 39 for metering the desired quantity of purified water through line 37 and valve 40 into enclosure or tube 41 which is sealed on one end and has the open end of the enclosure 41 connected to line 37.

The method of producing a shearable capsule using the apparatus of FIG. 1 will now be described with reference to FIG. 1. The first step involves introducing a selected amount of a gaseous radioisotope and a diluent into a mixing zone and in FIG. 1 the mixing zone is vessel 11 and line 12 up to valve 19. The top plate 42 of the chamber 14 is removed by removing the removable bolts from the top plate 42 on chamber 14 and withdrawing the piston 17. A glass ampoule is placed in the chamber 14 and the ampoule contains a measured quantity of radioisotope, preferably a xenon radioisotope such as xenon-133 and xenon-I27, usually a quantity of about I to about 8 curies. The piston 17,

top plate 42 and bolts are replaced so that the chamber 14 is sealed with piston 17 in the up position. Next valves 15, 19, 22 and 28 are opened and the vacuum pump 30 is used to pump the portion of lines 25, 21 and 12 thus opened to the pump 30 down to about to about 20 microns pressure as measured on the Hastings pressure gauge 29. Then valves 28, 22, 19 and are closed, and the screw piston 17 is turned down until the piston 17 comes in contact and crushes the glass ampoule in chamber 14 allowing the radioisotope in the ampoule to expand into the volume defined by the portion of chamber 14 below piston 17 and the portion of line 12 between valves 15 and 19. The screw piston 17 is then raised to the top of chamber 14.

A selected amount of a gaseous diluent (e.g. medical grade breathing air) is introduced into the mixing zone. The supply 33 of diluent in line 31 is adjusted to 0.5 psi pressure by closing valve 28 and opening valves 22 along with adjusting a pressure regulator on supply 33 to reach this pressure. The pressure is read on vacuum/pressure gauge which is capable of a reading of super atomospheric and subatmospheric pressure (i.e., pressure greater than atmospheric pressure and pressure less than atmospheric pressure). After the pressure is adjusted, valve 19 is opened and then closed so that the chamber 14 and the portion of line 12 between valves 15 and 19 is filled with the diluent as well as the radioisotope. Now valve 15 is opened and the screw piston 17 is screwed down, transferring the radioisotope and diluent to the mixing vessel 11. Valve 15 is closed and screw piston 17 is raised. Valve 19 is opened and closed again to let in further diluent to the portion of line 12 between valves 15 and 19 and chamber 14. Valve 15 is opened to transfer the diluent and any residual radioisotope to mixing vessel 11. This procedure is repeated until the predetermined volume of diluent is introduced with the radioisotope. The quantity of diluent is determined by the final curies of radioisotope desired for the mixture, the number of gas capsules to be made and the concentration of radioisotope per quantity of diluent desired.

The next step involves mixing the radioisotope and the diluent in the mixing zone 11 so that a homogeneous mixture is achieved. It is important that the radioisotope and diluent be in the form of a homogeneous mixture. This homogeneous mixture allows accurate aliquoting of premeasured patient doses of the mixture into the gas impermeable enclosure ultimately forming the capsule. When the radioisotope is xenon and the diluent is medical grade air, the radioisotope and diluent are slow to mix and mechanical agitation is used to expedite this mixing. in FIG. 1 this mixing is acccomplished by raising the screw piston 17 in chamber 14 to the upward most position (against top plate 42) and moving the movable piston 13 in vessel 11 up and down while valve 15 is open and valve 19 is closed.

The movement of the radioisotope and diluent between chamber 14 and vessel 11 is sufficient to give a mixing action resulting in a radioisotope-diluent mixture after about 20 cycles with the movable piston 13. In another embodiment it is possible to connect a bellows pump with mixing vessel 11 and use the bellows pump for achieving a mixture. The mixture is stored in chamber 14 after the mixing step is complete.

The next step involves discharging the mixture of diluent and radioisotope into a gas impermeable enclosure such as an organic material including polyethylene-terephthalate, vinyl-vinylidene chloride and polysulfone. This is done to give test capsules which are used to check the capsules for millicuries of radioisotope per capsule. A portion of the system is evacuated by opening valves 28 and 22 and pump 30 is used to evacuate the system. Then valves 22 and 28 are closed and the enclosure 41 sealed on one end is placed on the end of line 37 and sealed to line 37 with a Veeco fitting or similar means which makes a temporary seal of the enclosure 41 to line 37. The other end of the enclosure 41 has previously been sealed using a radiofrequency sealer or welder. The enclosure 41 is evacuated to 29 inches mercury by opening valves 26 and 28 and using pump 30 or by using a special mechanical pump that can be attached in a manner to draw on line 37. Valves 19 and 24 are then opened to let the diluentradioisotope mixture into the enclosure 41. The screw piston 17 is then lowered in chamber 14 until the pressure in the chamber 14, line 12 and the enclosure 41 is at a pressure selected from the range of O to 2 psi as indicated on gauge 20. Segments ultimately forming capsules are then sealed at regular intervals, usually at intervals of about 2 inches on the enclosure 41 by using a radiofrequency sealer to seal the enclosure to give a weld with each capsule containing about 1.5cc of the mixture. The thickness of the weld is usually about A to about inch so that the enclosure can then be cut with scissors and the segments become individual capsules about 2 inches in length. The xenon gas capsules are then measured for millicuries of xenon-l 33 per capsule in a gross ionization chamber to perform quality control check on the capsules. This completes the description of the last two steps of the method, namely sealing the gas impermeable enclosure into segments of a selected size and separating the segments into individual capsules.

After testing as discussed in the preceding paragraph, the stub of the enclosure 41 is removed from line 37 after valves 19 and 24 are closed and the production of capsules is commenced as previously done for the test capsules. During production, a long segment of the enclosure (or tube) 41 is used that has been sealed on the end not attached to line 37. The enclosure 41 is evacuated, either by pump 30 or by use of another mechanical pump inserted in line 37 as previously described above. Again valves 19 and 24 are opened to fill enclosure 41 with the mixture of radioisotope and diluent to a pressure selected from the range of O to 2 psi as indicated on the gauge 20.

When it is desired to insert a quantity of water such as a droplet of water, valve 40 is opened and about 0.2 to about 0.3 cubic centimeter of water is added by pushing down on the plunger of the automatic pipette syringe 39 which is fed by purified water from source 38. The droplet of water falls to the lower end of the tube 41 and a segment is sealed off at a mark by a radiofrequency sealer, usually to give a two inch segment or capsule as described above. Another 0.2 to 0.3 cubic centimeters of water is added by pushing down on syringe 39 and a second segment is sealed by the radiofrequency sealer. This process is repeated until all of the enclosure 41 is sealed into segments containing the gas mixture of a radioisotope and the diluent along with water (where desired). The enclosure 41 is cut at each seal in a manner avoiding rupture of the radioisotope containing capsules. After the last capsule is cut, valves 40 and 24 are closed and the stub of the enclosure 41 is evacuated by opening valves 26 and 28 to use pump 30 or by use of a mechanical pump inserted to draw on line 37. Then another enclosure 41 is attached, evacuated and filled by the same procedure as described above until the desired number of capsules is prepared. If more of the mixture of the radioisotope and diluent is needed, the procedure described above for mixing the radioisotope and the diluent is followed.

The gas capsules are examined over a light to insure that the water droplet is present in the capsule and that there are no visual defects in the capsule. The gas capsules are placed in a desiccator and evacuated to 25 inches of water for about minutes to evacuate any capsules that are leaking. The gas capsules are then assayed by individually placing the capsule in a radiation detection instrument such as a gross ionization chamber, and the acceptable gas capsules are then sampled for quality control before being prepared for shipment.

Various methods of sealing the gas impermeable enclosure into segments of a selected size can be practiced in addition to radiofrequency welding including heat impulse welding and ultrasonic welding.

FIG. 2 presents the apparatus for a method using a gas cylinder for transferring the radioisotope into the enclosure 4! with like numbers being used for the same components presented above in FIG. 1. Here a gas cylinder 50 is connected with line 12 between the chamber 14 and the mixing vessel 11. An additional valve 54 is provided in line 12 between cylinder 50 and vessel 11 to interrupt flow from the cylinder 50 to vessel 11. Line 51 is provided intersecting line 12 at a point between vessel 11 and valve 54 and at a point between valve 15 and screen 16. Line 51 has valve 52 to control flow through line 51. A U-tube 53 is provided in line 12 along with freezing means 56 (eg, a liquid nitrogen container) to freeze the radioisotope in U-tube 53 after release from cylinder 50.

The portion of the procedure using the apparatus of FIG. 2 which differs from the procedure using the apparatus of FIG. 1 will now be described. The system is evacuated to about to about 20 microns by opening valves 28, 22, l9, 15, 54 and 52 and using pump 30 while leaving valves 24, 26 and 32 closed. Valves 28, 22, l9, I5, 54 and 52 are then closed, and the gas cylinder 50 is opened to the U-tube 53 and the radioisotope is frozen into U-tube 53 by liquid nitrogen in freezing means 56. The cylinder 50 is closed and valve is opened followed by removal of the freezing means 56 from U-tube 53. As the U-tube 53 warms, the radioisotope expands into chamber 14. The diluent is then added from supply 33 by opening valves 32, 22, and 19 to let sufficient diluent into chamber 14 and line 12. The radioisotope and diluent in chamber 14 and line 12 is transferred back and forth through either open valve 52 in line 51 to vessel 1! or through open valve 15, U- tube 53 and open valve 54 to vessel 11 for a suitable number of times to achieve a mixture of the radioisotope-diluent. Preferably there is one transfer through open valve 15, U-tube 53 and open valve 54 to vessel 11 to insure any trapped radioisotope is flushed from line 12 and U-tube 53 into vessel 11. The radioisotope-diluent mixture is sampled, assayed and put into capsules similar to the procedure described above for FIG. 1.

When the gas cylinder 50 is emptied and must be changed for a new full cylinder, valves 15 and 54 are closed, and cylinder 50 is then replaced.

The capsule produced by the practice of this invention is comprised of a shearable, gas impermeable enclosure which contains a gaseous radioisotope useful for medical applications. Various materials meet the gas impermeable requirement of this invention and are capable of being readily sheared to release the gas with representative materials including polyethyleneterephthalate, vinyl-vinylidene chloride and polysulfone.

Various gaseous radioisotopes can be used in the practice of this invention and are sealed in the enclosure of the capsule produced by the practice of this invention. A preferred radioisotope is a xenon radioisotope including xenon-I27, xenon-I33, and xenonl29m. Other gaseous radioisotopes can be used including radon-222 and kyrpton-85. The person skilled in the art will realize that various gaseous radioisotopes can be selected and used depending upon the particular medical application at hand.

For certain medical applications it may be desirable to include a diluent with the gaseous radioisotope in the capsule 23. Representative diluents are air. nitrogen, medical grade air or oxygen. Moisture or water vapor or other physiologically benign absorbents for radiolysis products of the capsule enclosure material also may be added.

As will be apparent to those skilled in the art, various modifications and changes may be made in the invention described herein. It is accordingly the intention that the invention be construed in the broadest manner within the spirit and scope as set forth in the accompanying claims.

What is claimed is:

1. A method of manufacturing a capsule comprising a shearable gas impermeable enclosure having therein a gaseous radioisotope comprising the steps of a. introducing the gaseous radioisotope and a gaseous diluent into a mixing zone,

b. mixing the radioisotope and the diluent in the mixing zone,

c. discharging the mixture of step (b) into a gas impermeable enclosure sealed on one end,

cl. sealing the gas impermeable enclosure into segments of a selected size, and

e. separating the segments into individual capsules.

2. A method according to claim 1 in which the radioisotope is xenon.

3. A method according to claim 2 in which the xenon radioisotope is comprised of xenon-133.

4. A method according to claim 2 in which the xenon radioisotope is comprised of xenon-127.

5. A method according to claim 2 in which the xenon radioisotope is comprised of xenon-l29m.

6. A method according to claim 1 in which the radioisotope is comprised of krypton-85.

7. A method according to claim 1 in which the diluent is comprised of nitrogen.

8. A method according to claim 1 in which the diluent is comprised of air.

9. A method according to claim 1 in which the diluent is comprised of medical grade air.

10. A method according to claim 1 in which the enclosure is a plastic container comprised of vinylvinylidene chloride.

11. A method according to claim 10 further including the additional step of introducing moisture into the enclosure which is a plastic container.

9 l 12. A method according to claim 1 in which the ening step is conducted by radiofrequency welding. closure is a plastic container comprised of polyethy- 15. A method according to claim 1 in which the seallene-terephthalate. ing step is conducted by heat impulse welding.

13. A method according to claim 1 in which the en- 16. A method according to claim 1 in which the sealclosure is a plastic container comprised of polysulfone. 5 ing step is conducted by ultrasonic welding.

14. A method according to claim 1 in which the seal- 

1. A METHOD OF MANUFACTURING A CAPSULE COMPRISING A SHEARABLE GAS IMPPERMEABLE ENCLOSURE HAVING THEREIN A GASEOUS RADIOISOTOPE COMPRISING THE STEPS OF A. INTRODUCING THE GASEOUS RADIOISOTOPE AND A GASEOUS DILUENT INTO A MIXING ZONE, B. MIXING THE RADIOISOTOPE AND THE DILUENT IN THE MIXING ZONE, C. DISCHARGING THE MIXTURE OF STEP (B) INTO A GAS IMPERMEABLE ENCLOSURE SEALED ON ONE END, D. SEALING THE USE IMPERMEABLE ENCLOSURE INTO SEGMENTS OF A SELECTED SIZE, AND E. SEPARATING THE SEGMENTS INTO INDIVIDUAL CAPSULES.
 2. A method according to claim 1 in which the radioisotope is xenon.
 3. A method according to claim 2 in which the xenon radioisotope is comprised of xenon-133.
 4. A method according to claim 2 in which the xenon radioisotope is comprised of xenon-127.
 5. A method according to claim 2 in which the xenon radioisotope is comprised of xenon-129m.
 6. A method according to claim 1 in which the radioisotope is comprised of krypton-85.
 7. A method according to claim 1 in which the diluent is comprised of nitrogen.
 8. A method according to claim 1 in which the diluent is comprised of air.
 9. A method according to claim 1 in which the diluent is comprised of medical grade air.
 10. A method according to claim 1 in which the enclosure is a plastic container comprised of vinylvinylidene chloride.
 11. A method according to claim 10 further including the additional step of introducing moisture into the enclosure which is a plastic container.
 12. A method according to claim 1 in which the enclosure is a plastic container comprised of polyethylene-terephthalate.
 13. A method according to claim 1 in which the enclosure is a plastic container comprised of polysulfone.
 14. A method according to claim 1 in which the sealing step is conducted by radiofrequency welding.
 15. A method according to claim 1 in which the sealing step is conducted by heat impulse welding.
 16. A method according to claim 1 in which the sealing step is conducted by ultrasonic welding. 